It is important in the pharmaceutical field to identify an optimum composition, preparation and/or solid state phase. For example, on the occasion of crystallizing an active pharmaceutical ingredient (API) solely, when formed into a pharmaceutical composition, there may be the case where its stability or solubility or the like is not suited. In such a case, it is attempted to improve the stability or solubility or the like by forming a complex of API with other compound and crystallizing it to prepare a complex crystal (crystal of salt or cocrystal).
As a method for forming a complex of an objective compound with other compound and crystallizing it to prepare a complex crystal, a means for forming a salt of the objective compound with other compound and crystallizing it is a first alternative. In addition, there are also present “compounds which are unable to form a salt, such as neutral compounds having no dissociable group”, “compounds which even when forming a salt, do not bring about satisfactory improving effects”, or “compounds of which physical properties become inappropriate by the formulation of salts”. In such a case, a means for forming a cocrystal of the objective compound with other compound is exemplified as a second alternative.
In general, it is difficult to estimate what combination of compounds is suitable for obtaining an appropriate complex crystal. In particular, different from the crystal of salt, as for the cocrystal, it is difficult to estimate even what combination of compounds forms a complex. Under such circumstances, in order to find out an optimum complex crystal, a massive number of combinations of compounds shall be tried. Therefore, a simple and rapid method for screening a complex crystal is required.
As a method for screening a cocrystal, a method for preparing a suspension mixture using a variety of solvents (slurry method) is known (Non-Patent Document 1). In addition, a method for screening a cocrystal by completely dissolving it in a solvent is known (Patent Documents 1 and 2).